Methyl iodide → HCID 58827278, compound

HRID 448413Notes

Reaction equation

HRID 448413 reaction equation
[O:1]=[C:2]1[CH:7]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[NH:18][CH2:19][C:20]([OH:22])=[O:21])[C:9]2=[O:23])[CH2:6][CH2:5][C:4](=[O:24])[NH:3]1.CI.[C:27](=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(Cl)Cl>[CH3:27][O:21][C:20](=[O:22])[CH2:19][NH:18][C:14]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:15]=1[C:16](=[O:17])[N:8]([CH:7]1[CH2:6][CH2:5][C:4](=[O:24])[NH:3][C:2]1=[O:1])[C:9]2=[O:23]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 58827328N-[2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]glycine

Product 1

HCID 58827278HCID 58827278, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of [2-(2,6-dioxopiperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylamino]acetic acid (0.66 g, 2.0 mmol) in DMF (20 mL), were added methyl iodide (0.34 g, 2.4 mmol) and potassium carbonate (0.33 g, 2.4 mmol). The mixture was stirred overnight at room temperature. The solvent was evaporated in vacuo, giving a yellow oil. The oil was dissolved in CH2Cl2 (100 mL), washed with sat. aq. sodium bicarbonate (100 mL), water (100 mL) and brine (100 mL), and dried (MgSO4). The solvent was evaporated in vacuo to give a yellow solid. This material was triturated with diethyl ether and then filtered, and the resulting solid was chromatographed, eluting with 9:1 methylene chloride-ethyl acetate. The resulting solid was triturated in 1:1 ethyl ether-water, filtered, and dried under high vacuum, providing 0.42 g (61%) of the product as a yellow solid: mp 210-212° C.; 1H NMR (DMSO-d6) δ 2.03-2.07 (m, 1H), 2.47-2.63 (m, 2H), 2.96-2.83 (m, 1H), 3.69 (s, 3H), 4.23 (d, J=6.0 Hz, 2H), 5.08 (dd, J=12.4 Hz, J=5.2 Hz, 1H), 6.91-7.11 (m, 3H), 7.61 (t, J=7.7 Hz, 1H), 11.12 (s, 1H); 13C NMR (DMSO-d6) δ 22.10, 30.96, 43.62, 48.51, 51.90, 109.76, 111.22, 117.65, 132.01, 136.09, 145.76, 167.21, 168.70, 170.12, 170.65, 172.77; Anal. calcd. for C16H15N3O6: C, 55.65; H, 4.38; N, 12.17. Found: C, 55.64; H, 4.28; N, 11.98.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customgiving a yellow oil
  3. washwashed with sat. aq. sodium bicarbonate (100 mL), water (100 mL) and brine (100 mL)
  4. dry with materialdried (MgSO4)
  5. customThe solvent was evaporated in vacuo
  6. customto give a yellow solid
  7. customThis material was triturated with diethyl ether
  8. filtrationfiltered
  9. customthe resulting solid was chromatographed
  10. washeluting with 9:1 methylene chloride-ethyl acetate
  11. customThe resulting solid was triturated in 1:1 ethyl ether-water
  12. filtrationfiltered
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-e936047ac4ce4bcdb8e6b4e8eb1cec6d
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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